Pharmacokinetics, Distribution and Excretion of PNA in Rat by Liquid Chromatography Mass Spectrometry Method

Abstract

The pharmacokinetic profiles, tissue distribution and excretion patterns of PNA in healthy male and female Sprague-Dawley rats following a single intra-duodenum administration were investigated by previously established LC-MS method. Absorption was rapid in rats as evidenced by a short time to maximum concentration (C_max) of 0.050±0.021, 0.072±0.017 and 0.067±0.018 h at the 25, 50 and 100 mg/kg dose level, respectively. The C_max were 754.9±196.1, 1187.8±642.1 and 2082.1±1278.5 ng/mL and the AUC_0-4 were 71.8±25.9, 135.2±69.9 and 303.3±198.3 µg/L*h, which showed linear with the intra-duodenum administration range from 25–100 mg/kg. Tissues were collected at 4 time points (3, 10 min, 1 and 3 h) after dosing at 50 mg/kg. Compare to the concentrations of plasma and other tissues, the level was particularly high in the liver and brain during 3 h. Bile/urine and feces samples were collected before dosing and till 24/48 h post-dosing. The mean cumulative excretion of unchanged PNA in bile amounted to 0.021% of the dose up to 24 h. The mean recoveries of unchanged PNA were 0.0095% and 0.043% of the dose up to 48 h in urine and feces, respectively. There was no significant difference in PNA concentration observed between male and female rats during the experiments.

Key words

liquid chromatography/mass spectrometry - PNA - pharmacokinetics - tissue distribution - excretion

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